Vratislav Strnad, M.D.
Dr. Vratislav Strnad and Dr. Csaba Polgár outline the case for APBI
July 26, 2016
By Dr. Vratislav Strnad and Dr. Csaba Polgár
For decades, women with early-stage breast cancer have been treated with external whole breast irradiation (WBI), where high-dose radiation is delivered to the entire breast from outside the body over the course of five to six weeks. As our understanding of breast cancer evolved, and based on the observation that most breast cancers recur close to the original tumor bed, clinicians began randomized trials to evaluate if a shorter course of therapy, treating only the cancerous part of the breast, could reduce side effects common to WBI while maintaining adequate cancer control. Accelerated partial breast irradiation with brachytherapy (APBI brachytherapy) involves a four- to five-day postoperative course of radiotherapy delivered into the breast cavity following a lumpectomy.
Recent large-scale prospective clinical studies evaluating this technique add to an established and growing body of evidence that APBI brachytherapy is a safe and effective alternative to WBI with fewer late side effects and improved cosmetic outcomes.
GEC-ESTRO overview
The Groupe Européen de Curiethérapie European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) trial is an ongoing European multicenter prospective study to assess the role of APBI brachytherapy alone compared to WBI, with a boost in a defined group of patients with invasive (stage I-IIA) breast cancer or ductal carcinoma in situ (DCIS; stage 0) who underwent breast-conserving surgery. Researchers evaluated 1,184 patients aged 40 years and above who were randomized to a standardized treatment arm (WBI, n=551) or an investigational treatment arm (APBI, n=633). Patients received follow-up examinations every three months initially and annually after 60 months. The median age of enrolled patients was 62 years old, with a median post-treatment follow up period of 6.6 years.
Key study takeaways
Benefit No. 1: APBI is clinically equivalent to WBI, with significantly reduced treatment time.
Investigators found adjuvant APBI with brachytherapy after breast conserving surgery is not inferior to adjuvant WBI with a boost for selected patients with early breast cancer, with equivalent local recurrence rates observed with both treatment modalities. At five-year follow-up, nine patients treated with APBI and five patients treated with WBI had a local recurrence, equating to cumulative recurrence rates of 1.44 percent and 0.92 percent (p=0.42), respectively. No significant differences in regional and distant recurrences were observed between groups.
Benefit No. 2: APBI is associated with a low incidence of serious late side effects, with a significantly lower risk of Grade 2-3 breast pain.
Study results demonstrated a low incidence of all serious late side effects (approximately 3 percent in both arms). Importantly, the risk of grade 2-3 breast pain was significantly lower in patients treated with APBI (1.14 percent vs. 3.17 percent; p=0.0389). No grade 4 late side effects were reported and no difference in mastectomy rates was observed between arms.
Benefit No. 3: APBI associated with fewer late skin effects and improved cosmetic outcomes.
The five-year toxicity profile was similar for patients treated with breast conserving surgery followed by either APBI using interstitial multicatheter brachytherapy or conventional WBI with tumor bed boost. However, a trend toward fewer late skin side effects and better cosmetic results was observed in the APBI arm, with significantly more patients (43.6 percent vs. 30.9 percent; p=0.0002) experiencing excellent cosmetic results.
Conclusions
Early-stage breast cancer remains a disease with high unmet medical needs that places an enormous physical, emotional and economic burden on women, families and health care systems. These robust data, representing the largest randomized prospective study of its type ever conducted to date, confirm previous studies that show patients treated by a short course of APBI with multicatheter brachytherapy experience equivalent rates of recurrence, disease-free survival, overall survival and toxicity compared to those receiving a traditional longer course of external whole breast irradiation, with better cosmetic outcomes.
The findings are expected to drive significant changes in how clinicians approach early stage breast cancer treatment in patients 40 years and above and place APBI multicatheter brachytherapy as an accepted standard alternative to whole breast irradiation. The American Society for Radiation Oncology (ASTRO), the leading radiation oncology professional group in the U.S., has made an initial recommendation to lower the age of “suitable” candidates for APBI to 50, and the society’s professional guidelines are expected to be officially updated in the coming months.
About the authors: Professor Vratislav Strnad, M.D., Ph.D., is chair of the GEC-ESTRO Brachytherapy Working Group and radiation oncologist at the Department of Radiation Oncology of University Hospital, Erlangen, Germany. Csaba Polgár, M.D., Ph.D., M.Sc., is a professor and head of the Radiotherapy Center at the Hungarian National Institute of Oncology, Budapest, council member of GECESTRO and co-lead study author.
For decades, women with early-stage breast cancer have been treated with external whole breast irradiation (WBI), where high-dose radiation is delivered to the entire breast from outside the body over the course of five to six weeks. As our understanding of breast cancer evolved, and based on the observation that most breast cancers recur close to the original tumor bed, clinicians began randomized trials to evaluate if a shorter course of therapy, treating only the cancerous part of the breast, could reduce side effects common to WBI while maintaining adequate cancer control. Accelerated partial breast irradiation with brachytherapy (APBI brachytherapy) involves a four- to five-day postoperative course of radiotherapy delivered into the breast cavity following a lumpectomy.
Recent large-scale prospective clinical studies evaluating this technique add to an established and growing body of evidence that APBI brachytherapy is a safe and effective alternative to WBI with fewer late side effects and improved cosmetic outcomes.
GEC-ESTRO overview
The Groupe Européen de Curiethérapie European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) trial is an ongoing European multicenter prospective study to assess the role of APBI brachytherapy alone compared to WBI, with a boost in a defined group of patients with invasive (stage I-IIA) breast cancer or ductal carcinoma in situ (DCIS; stage 0) who underwent breast-conserving surgery. Researchers evaluated 1,184 patients aged 40 years and above who were randomized to a standardized treatment arm (WBI, n=551) or an investigational treatment arm (APBI, n=633). Patients received follow-up examinations every three months initially and annually after 60 months. The median age of enrolled patients was 62 years old, with a median post-treatment follow up period of 6.6 years.
Csaba Polgár, M.D.
Key study takeaways
Benefit No. 1: APBI is clinically equivalent to WBI, with significantly reduced treatment time.
Investigators found adjuvant APBI with brachytherapy after breast conserving surgery is not inferior to adjuvant WBI with a boost for selected patients with early breast cancer, with equivalent local recurrence rates observed with both treatment modalities. At five-year follow-up, nine patients treated with APBI and five patients treated with WBI had a local recurrence, equating to cumulative recurrence rates of 1.44 percent and 0.92 percent (p=0.42), respectively. No significant differences in regional and distant recurrences were observed between groups.
Benefit No. 2: APBI is associated with a low incidence of serious late side effects, with a significantly lower risk of Grade 2-3 breast pain.
Study results demonstrated a low incidence of all serious late side effects (approximately 3 percent in both arms). Importantly, the risk of grade 2-3 breast pain was significantly lower in patients treated with APBI (1.14 percent vs. 3.17 percent; p=0.0389). No grade 4 late side effects were reported and no difference in mastectomy rates was observed between arms.
Benefit No. 3: APBI associated with fewer late skin effects and improved cosmetic outcomes.
The five-year toxicity profile was similar for patients treated with breast conserving surgery followed by either APBI using interstitial multicatheter brachytherapy or conventional WBI with tumor bed boost. However, a trend toward fewer late skin side effects and better cosmetic results was observed in the APBI arm, with significantly more patients (43.6 percent vs. 30.9 percent; p=0.0002) experiencing excellent cosmetic results.
Conclusions
Early-stage breast cancer remains a disease with high unmet medical needs that places an enormous physical, emotional and economic burden on women, families and health care systems. These robust data, representing the largest randomized prospective study of its type ever conducted to date, confirm previous studies that show patients treated by a short course of APBI with multicatheter brachytherapy experience equivalent rates of recurrence, disease-free survival, overall survival and toxicity compared to those receiving a traditional longer course of external whole breast irradiation, with better cosmetic outcomes.
The findings are expected to drive significant changes in how clinicians approach early stage breast cancer treatment in patients 40 years and above and place APBI multicatheter brachytherapy as an accepted standard alternative to whole breast irradiation. The American Society for Radiation Oncology (ASTRO), the leading radiation oncology professional group in the U.S., has made an initial recommendation to lower the age of “suitable” candidates for APBI to 50, and the society’s professional guidelines are expected to be officially updated in the coming months.
About the authors: Professor Vratislav Strnad, M.D., Ph.D., is chair of the GEC-ESTRO Brachytherapy Working Group and radiation oncologist at the Department of Radiation Oncology of University Hospital, Erlangen, Germany. Csaba Polgár, M.D., Ph.D., M.Sc., is a professor and head of the Radiotherapy Center at the Hungarian National Institute of Oncology, Budapest, council member of GECESTRO and co-lead study author.